Cancer: Prostate, breast, endometrial
Action: Anti-estrogenic effects, radio-protective effect, pneumonitis, cachexia-inhibiting
Prostate Cancer, Breast Cancer
Isoflavones have been investigated in detail for their role in the prevention and therapy of prostate cancer. This is primarily because of the overwhelming data connecting high dietary isoflavone intake with reduced risk of developing prostate cancer. A number of investigations have evaluated the mechanism(s) of anti-cancer action of isoflavones such as genistein, daidzein, biochanin A, equol, etc., in various prostate cancer models, both in vitro and in vivo.
Nuclear receptors are considered to be a central goal for maximizing treatment opportunities in breast cancer. Among natural ligands for estrogen receptors (ER and ERβ), which are members of the nuclear receptors super-family, are found isoflavones. These natural compounds have a similar structure to the main female hormone 17β-estradiol. A rich source of isoflavones is soy and its products. Three isoflavones of the aglycone form (genistein, daidzein, glycitein) are predominantly found in soybean and red clover. Other important isoflavones are biochanin A and formononetin (Bialešová et al., 2013).
Breast Cancer
Soy isoflavones do not function as an estrogen, but rather exhibit anti-estrogenic properties. However, their metabolism differs between humans and animals and therefore the outcomes of animal studies may not be applicable to humans. The majority of breast cancer cases are hormone-receptor-positive; therefore, soy isoflavones should be considered a potential anti-cancer therapeutic agent (Douglas et al., 2013).
Anti-cancer Effects
Use of soy isoflavone mixture has been advocated as an alternative, wherein daidzein can negate harmful effects of genistein. Recent research indicates the novel role of genistein and other isoflavones in the potentiation of radiation therapy, epigenetic regulation of key tumor suppressors and oncogenes, and the modulation of miRNAs, epithelial-to-mesenchymal transition, and cancer stem cells, which has renewed the interest of cancer researchers in this class of anti-cancer compounds (Ahmad et al. 2013).
Radiation-induced Pneumonitis, Radiation-induced Side-effects
Radiation-induced pneumonitis and fibrosis have restricted radiotherapy for lung cancer. In a preclinical lung tumor model, soy isoflavones showed the potential to enhance radiation damage in tumor nodules and simultaneously protect normal lung from radiation injury. Soy isoflavones given pre- and post-radiation protected the lungs against adverse effects of radiation including skin injury, hair loss, increased breathing rates, inflammation, pneumonitis and fibrosis, providing evidence for a radio-protective effect of soy (Hillman et al., 2013 a).
Radio-sensitizer
Combined soy and radiation caused a significantly stronger inhibition of tumor progression compared to each modality alone in contrast to large invasive tumor nodules seen in control mice. At the same time, soy reduced radiation injury in lung tissue by decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and vessels (Hillman et al., 2013 b).
Endometrial Cancer
Because of their anti-oxidant and anti-mutagenic properties, flavonoids may reduce cancer risk. Some flavonoids have anti-estrogenic effects that can inhibit the growth and proliferation of endometrial cancer cells. The intake of flavanols, flavanones, flavonols, anthocyanidins, flavones, isoflavones, and proanthocyanidins was measured and high consumption of selected proanthocyanidins may reduce endometrial cancer risk (Rossi et al., 2013).
Breast Cancer Protection
The evidence to date from observational epidemiologic studies, suggests that soy food intake, in the amount consumed in Asian populations (about 10 to 20 mg isoflavones per day), may be associated with a reduction of risk of breast cancer development as well as mortality and recurrence among women with breast cancer. The large number of clinical intervention studies on soy that have investigated intermediate biomarkers of breast cancer risk, including circulating estrogen levels, mammographic density, and breast tissue changes (cell proliferation), have not shown clear beneficial or deleterious effects (Wu et al., 2013).
Cachexia-Inhibiting
Isoflavones possess anti-proliferative effects of cachexia-inducing cells (MKN45cl85 and 85As2mLuc) cancer cell lines. Isoflavone treatment on the models induced tumor cytostasis, attenuation of cachexia, and prolonged survival whereas discontinuation of the treatment resulted in progressive tumor growth and weight loss (Yanagihara et al., 2013).
Methylation Effects
There is an inverse correlation between estrogenic marker complement (C)3 and genistein, which suggests an anti-estrogenic effect. Isoflavones induced dose-specific changes in RARβ2 and CCND2 gene methylation, which correlated with genistein levels. Research by Qin & Zhu (2009) provides novel insights into estrogenic and methylation effects of dietary isoflavones.
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